MINIR-II: Minimally Invasive Neurosurgical Intracranial Robot

描述（由申请人提供）：该R 01项目建立在一个非常成功的R21项目的基础上，该项目涉及使用形状记忆合金（SMA）致动器的微创神经外科颅内机器人（MINIR-I）的开发和可行性，以及在连续MRI下对该器械切除猪脑中植入的“转移瘤”的评价。 在我们实现R21项目的具体目标的同时，我们也发现了新的挑战，这是R 01应用的基础。 脑肿瘤是最可怕的癌症并发症之一，发生在20-40%的成年癌症患者中。 尽管治疗取得了许多进展，但这些患者的预后很差，中位生存期为4-8个月。 无论是原发性（内在）恶性肿瘤还是继发性（转移性）恶性肿瘤，癌症患者的脑受累都是毁灭性的，因为它威胁到个体的个性和身份，并且总是最有可能直接和严重影响生活质量的所有并发症。 目前，大多数脑肿瘤的最佳治疗包括原发性手术切除，以促进辅助治疗，如放射和化疗。 不幸的是，许多患者由于病变的不利位置（通常较深或以其他方式无法使用常规神经外科技术）和患者的一般健康状况差而不能进行脑肿瘤的初次手术切除。 为了解决这个问题，基于我们R21试点项目的成功以及从中吸取的经验教训，我们建议开发完全MRI兼容的MINIR-II，并通过对临床相关的离体和体内猪以及随后的人尸体模型进行全面评估来证明MINIR-II的安全性和有效性。 根据设想，MINIR-II将在医生的直接控制下，仅从实时MRI获得靶向信息，该MRI使用嵌入MINIR-II内的传感器的主动靶向方法。 为了实现MINIR-II，我们将实现四个具体目标：1）设计完全MRI兼容的刚性塑料体的多自由度（DOF）MINIR-II，其具有线缆驱动接头、用于布线和电子器件的中空内芯、冲洗和抽吸能力以及肿瘤去除能力，2）开发和表征能够模制具有微型特征的几何形状复杂的机器人连杆的多件式模具，以生产完全一次性/单次使用的MINIR-II原型，3）开发MINIR-II的跟踪和导航系统，该系统将允许近端和远端结构的可视化，以准确靶向和切除肿瘤，最后4）MINIR-II在明胶体模和转移性脑肿瘤的临床相关模型（包括尸体猪模型、生猪模型和人尸体模型）中的安全性和有效性。 我们在这个项目结束时的目标是使MINIR-II（在连续MRI下运行）准备好进行临床试验。 公共卫生相关性：脑肿瘤是最可怕的癌症并发症之一，发生在20-40%的成年癌症患者中，中位生存期为4-8个月。 虽然初次手术切除是首选的方法，但大多数患者由于病变位置不利和一般健康状况不佳而无法接受此手术。 因此，本项目的目标是基于开发MINIR-I的R21试点项目的进展，开发完全兼容MRI的MINIR-II，其中MINIR-II将由刚性塑料主体制成，具有用于肿瘤切除的集成硬件，并将在连续MRI下操作。

DESCRIPTION (provided by applicant): This R01 project builds on a highly successful R21 project which involved the development and feasibility of a Minimally Invasive Neurosurgical Intracranial Robot (MINIR-I) using shape memory alloy (SMA) actuators as well as the evaluation of the device under continuous MRI for resection of an implanted "metastatic tumor" in swine brain. While we achieved the specific aims of the R21 project, we also discovered new challenges, which are the basis for this R01 application. Brain tumors are among the most feared complications of cancer occurring in 20-40% of adult cancer patients. Despite numerous advances in treatment, the prognosis for these patients is poor, with a median survival of 4-8 months. Whether a primary (intrinsic) malignancy, or a secondary (metastatic) malignancy, involvement of the brain in a cancer patient is devastating, because it threatens the very personality and identity of the individual, and is invariably the most likely of all complications o directly and severely affect the quality of life. Currently, the optimal treatment for most brain tumors involves primary surgical resection to facilitate adjuvant therapies such as radiation and chemotherapy. Unfortunately, many patients cannot undergo primary surgical resection of their brain tumor due to unfavorable location of the lesion (usually deep or otherwise inaccessible to conventional neurosurgical techniques), and poor general health of the patient. To address this problem, based on the success of our R21 pilot project, and the lessons learned therein, we propose to develop a fully MRI- compatible MINIR-II and demonstrate the safety and efficacy of MINIR-II through comprehensive assessments on clinically relevant ex vivo and in vivo swine and followed by human cadaver models. As envisioned, MINIR-II will be under the direct control of the physician, with targeting information obtained exclusively from real-time MRI that uses active targeting methods with the sensors embedded within MINIR-II. To realize MINIR-II, we will address four specific aims: 1) Design a fully MRI compatible multiple degree-of-freedom (DOF) MINIR-II of rigid plastic body with cable driven joints, hollow inner core for routing cablin and electronics, irrigation and suction capability, and tumor removal capability, 2) Develop and characterize a multi-piece mold capable of molding geometrically complex robot links with miniature features to produce a completely disposable/single use MINIR-II prototype, 3) Develop a tracking and navigation system for MINIR-II that will allow visualization of proximal and distal structures for accurate targeting and resection of the tumor, and finally 4) the safety and efficacy of MINIR-II in gelatin phantoms and clinically relevant models of metastatic brain tumor including, a cadaveric pig model, a live pig model, and a human cadaver model. Our goal at the end of this project is to have MINIR-II (operated under continuous MRI) ready for clinical trials. PUBLIC HEALTH RELEVANCE: Brain tumors are among the most feared complications of cancer occurring in 20-40% of adult cancer patients with a median survival of 4-8 months. Though primary surgical resection is the preferred approach, most patients cannot undergo this procedure due to an unfavorable location of the lesion and poor general health. Hence, the goal of this project is to develop fully MRI compatible MINIR-II based on the advances in the R21 pilot project for the development of MINIR-I, whereby MINIR-II will be made of a rigid plastic body with integrated hardware for tumor removal and will be operated under continuous MRI.